Influenza, MenACWY, HPV and COVID-19 vaccines in children: uptake, safety and effectiveness during the COVID-19 pandemic in the UK

Aims and Objectives:

The COVID-19 pandemic has affected millions of children globally with major health, social and educational consequences. It was seen that during the pandemic that fewer children received some of the common childhood vaccines. This might result in the resurgence of some infectious diseases which have so far been controlled by vaccines, especially as we returned to a normal life, with more people travelling, and social distance not being practiced. Drops in vaccination uptake can have a big impact on the health system and understanding why this is happening is important.

Whilst clinical trials and other studies have shown COVID-19 vaccines to be safe and effective in children, less is known on how safe and effective these vaccines are when administrated together with other common childhood vaccines, such as vaccines against influenza, meningitis and septicaemia (MenACWY) and human papillomavirus (HPV) vaccines. HPV is a virus that causes most cervical cancers. Parents and carers are asked to provide consent for their children to receive these vaccines, and they need more information to make a fully informed decision.

Using information routinely collected in healthcare records we can see what happens when these vaccines are given in the real world. We will look at how many children have received the influenza, MenACWY and HPV vaccine and if there were changes in the uptake rates before and during the COVID-19 pandemic.

Since concerns about vaccine safety can affect vaccine uptake, we will compare the risk of possible side effects of COVID-19 vaccination to the risk of possible side effects after Influenza, MenACWY or HPV vaccine. This information will help parents to put the safety of COVID-19 vaccination in children into context by comparing with the safety of other routine vaccinations. This will also be beneficial for parents, carers and young people beyond the pandemic context. We have selected a list of diseases to investigate which could be associated with each vaccination with the expertise of paediatricians and the guidance of parents/carers involved in this study.

We will find out how safe COVID-19 vaccines and other childhood vaccines (Influenza, MenACWY, HPV) are if they are given together on the same day or in a short window of time. We will also evaluate if combining two vaccines might have reduced their effectiveness against preventing hospital admissions.
We will make our findings publicly available using academic publications, through media releases and community groups to provide easily understandable and timely information for clinicians, parents, carers, young people and policy makers. We will ask our public representatives to help us produce materials to share our findings in an easy and clear way, such as through infographics. We will share results with relevant governmental bodies to help improve policymaking.

Research Methods:

Using information routinely collected in healthcare records is one way of seeing what happens when the vaccines are given in the real world. We will use anonymised GP and hospital records to look at how many children have had selected routine childhood vaccines (influenza, MenACWY and HPV) before and during the COVID-19 pandemic. We will investigate if there are any patterns in this that suggest possible inequalities in uptake, for example between different ethnic groups. We will also look at whether children were given a COVID-19 vaccine at the same time as one of these routine childhood vaccines.

We will study how safe the influenza, MenACWY and HPV vaccines are compared to COVID-19 vaccines in children. We will look at any possible adverse events that happened within 28 days (4 weeks) of having one of these vaccines, to make sure we are looking at events likely to be related to vaccination. For each type of vaccine, we will compare the risk for each child of having a possible adverse event in the 28 days after they had the vaccine to the risk of having a possible adverse event in a separate control time period (anytime from the beginning of the study to up to 29 days before they had the vaccine and from 29 days after having the vaccine). This approach will let us examine the effect of the vaccines alone, while other things that can affect the chance of having the adverse event are kept the same (or controlled). We will do exactly the same thing, looking at the risk of having a possible adverse event in the 28 days after having an influenza, meningitis or SARS-CoV-2 (COVID-19) infection. We will also compare the safety of receiving a COVID-19 vaccine at the same time as an influenza, MenACWY or HPV vaccine with the safety of receiving individual vaccines at different times.

We will investigate how effective the COVID-19 vaccines are against being admitted to hospital by taking two groups: children who have been admitted to hospital with COVID-19 (cases) with children who have not been admitted to hospital with COVID-19 (controls). We will look back retrospectively to see the rates of vaccinations in each group and compare them. To make the two groups as more similar as possible, we will select those children who have not been admitted to hospital with COVID-19 to have the same age, sex and GP practice of those children who have been admitted to hospital with COVID-19. We will repeat this analysis for the influenza and MenACWY vaccines and compare the effectiveness of these vaccines to that of COVID-19 vaccines. We will not assess HPV vaccine effectiveness in this study, as these vaccines aim to prevent cervical cancer, which is unlikely to be diagnosed until cervical screening begins at age 25.

Other outputs:

We will disseminate our results through channels that reach beyond the primarily academic audience of journal articles and will use the networks we have developed through our existing patient and public involvement (PPI) work to disseminate communication tools widely. We plan to create infographics and will employ translation and/or interpretation services if required. We will work with community organisations and health centres to disseminate our results through their channels, e.g., newsletters, noticeboards and meetings. We will also create informative videos to upload to social media platforms, such as YouTube, Instagram and TikTok, if this is found to be an appropriate strategy with our public contributors.

Implications:

This work will inform clinicians, parents/carers and young people on the safety of vaccinations for children. It will also inform policy makers such as the UK Joint Committee on Vaccination and Immunisation (JCVI) and medicines regulators such as Medicines and Healthcare products Regulatory Agency (MHRA). It will allow those considering whether to be vaccinated or not, or to provide consent for a child, to make informed decisions and may help to reduce health disparities through targeted vaccination campaigns.

Clinical outcomes which might indicate serious adverse events, comorbidities, demographics, exposures and relevant information of the patients (using SNOMED codes):

Demographics:
Sex
GP practice ID
Region of England
Townsend quintile
Ethnicity
Year of birth
Date left study population
Reason left study population
Date entered study population
BMI

Co-morbidities:
Chronic heart disease (congenital and acquired) (CHD)
Chronic respiratory disease (asthma, cystic fibrosis, ciliary dyskinesia, bronchopulmonary dysplasia)
Asplenia or dysfunction of the spleen
Chronic conditions of the kidney, liver or digestive system
Diabetes diagnosis (any type 1 and type 2 diabetes)
Chronic neurological disease (including neurodisability, neuromuscular disease, degenerative neurological conditions)
Learning Difficulties (excluding Down’s)
Down's syndrome
Neurodevelopmental disorders (e.g. autism and ADHD)
Mental Health (includes anxiety, depression and psychosis)
Epilepsy
COVID-19 risk score

Infection exposures:
HPV infection
COVID-19 positive test

Vaccine exposures:
Influenza vaccine
HPV vaccine
MenACWY vaccine
COVID-19 vaccine
Codes indicating vaccine refusal/declined

Drugs (confounders):
Antipsychotic drugs
Tricyclic and related antidepressant drugs
Monoamine-oxidase inhibitors
Compound antidepressant preparations
Other antidepressant drugs
Central nervous stimulants
Drugs used in control of epilepsy
Insulins (short-acting insulin preparations and intermediate and long-acting insulin preparations)
Oral hypoglycaemic drugs
Other hypoglycaemic drugs: glinide, GPL-1 agonist, acarbose or guar etc.


Suspected adverse events:
Fever
Anaphylaxis
Febrile seizures
Guillain-Barre syndrome
Headache
Injection site reactions
Myocarditis
Myositis
Rash
Wheezing/breathlessness

Clinical outcomes which might indicate serious adverse events, comorbidities (using ICD-10 codes), infection exposures

Co-morbidities:
Chronic heart disease (congenital and acquired)
Chronic respiratory disease (asthma, cystic fibrosis, ciliary dyskinesia, bronchopulmonary dysplasia)
Asplenia or dysfunction of the spleen
Chronic conditions of the kidney, liver or digestive system
Diabetes diagnosis (any type 1 and type 2 diabetes)
Chronic neurological disease (including neurodisability, neuromuscular disease, degenerative neurological conditions)
Learning Difficulties (excluding Down’s)
Down's Syndrome
Neurodevelopmental disorders (e.g. autism and attention deficit hyperactivity disorder)
Mental Health (includes anxiety, depression and psychosis)
Epilepsy

Infections:
Meningitis
Influenza
COVID-19

Suspected adverse events:
Febrile seizure
Fever
Guillain-Barre syndrome
Myocarditis
Myositis
Venous thromboembolism

Prof Julia Hippisley-Cox (University of Oxford)

Dr Defne Saatci (University of Oxford)

Professor Anthony Harnden (University of Oxford)

Dr Jennifer Hirst (University of Oxford)

Miss Emma Copland (University of Oxford)

Mrs Samina Begum

Professor Carol Coupland (University of Nottingham)